Physiology最新文献

{"title":"Mitochondrial Calcium Regulation of Cardiac Metabolism in Health and Disease.","authors":"Enrique Balderas, Sandra H J Lee, Neeraj K Rai, David M Mollinedo, Hannah E Duron, Dipayan Chaudhuri","doi":"10.1152/physiol.00014.2024","DOIUrl":"10.1152/physiol.00014.2024","url":null,"abstract":"<p><p>Oxidative phosphorylation is regulated by mitochondrial calcium (Ca²⁺) in health and disease. In physiological states, Ca²⁺ enters via the mitochondrial Ca²⁺ uniporter and rapidly enhances NADH and ATP production. However, maintaining Ca²⁺ homeostasis is critical: insufficient Ca²⁺ impairs stress adaptation, and Ca²⁺ overload can trigger cell death. In this review, we delve into recent insights further defining the relationship between mitochondrial Ca²⁺ dynamics and oxidative phosphorylation. Our focus is on how such regulation affects cardiac function in health and disease, including heart failure, ischemia-reperfusion, arrhythmias, catecholaminergic polymorphic ventricular tachycardia, mitochondrial cardiomyopathies, Barth syndrome, and Friedreich's ataxia. Several themes emerge from recent data. First, mitochondrial Ca²⁺ regulation is critical for fuel substrate selection, metabolite import, and matching of ATP supply to demand. Second, mitochondrial Ca²⁺ regulates both the production and response to reactive oxygen species (ROS), and the balance between its pro- and antioxidant effects is key to how it contributes to physiological and pathological states. Third, Ca²⁺ exerts localized effects on the electron transport chain (ETC), not through traditional allosteric mechanisms but rather indirectly. These effects hinge on specific transporters, such as the uniporter or the Na⁺/Ca²⁺ exchanger, and may not be noticeable acutely, contributing differently to phenotypes depending on whether Ca²⁺ transporters are acutely or chronically modified. Perturbations in these novel relationships during disease states may either serve as compensatory mechanisms or exacerbate impairments in oxidative phosphorylation. Consequently, targeting mitochondrial Ca²⁺ holds promise as a therapeutic strategy for a variety of cardiac diseases characterized by contractile failure or arrhythmias.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nrf2-Keap1 in Cardiovascular Disease: Which Is the Cart and Which the Horse?","authors":"Neha Dhyani, Changhai Tian, Lie Gao, Tara L Rudebush, Irving H Zucker","doi":"10.1152/physiol.00015.2024","DOIUrl":"10.1152/physiol.00015.2024","url":null,"abstract":"<p><p>High levels of oxidant stress in the form of reactive oxidant species are prevalent in the circulation and tissues in various types of cardiovascular disease including heart failure, hypertension, peripheral arterial disease, and stroke. Here we review the role of nuclear factor erythroid 2-related factor 2 (Nrf2), an important and widespread antioxidant and anti-inflammatory transcription factor that may contribute to the pathogenesis and maintenance of cardiovascular diseases. We review studies showing that downregulation of Nrf2 exacerbates heart failure, hypertension, and autonomic function. Finally, we discuss the potential for using Nrf2 modulation as a therapeutic strategy for cardiovascular diseases and autonomic dysfunction.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Insights into IGF-1 Signaling in the Heart.","authors":"Wang-Soo Lee, E Dale Abel, Jaetaek Kim","doi":"10.1152/physiol.00003.2024","DOIUrl":"10.1152/physiol.00003.2024","url":null,"abstract":"<p><p>Insulin-like growth factor-1 (IGF-1) signaling has multiple physiological roles in cellular growth, metabolism, and aging. Myocardial hypertrophy, cell death, senescence, fibrosis, and electrical remodeling are hallmarks of various heart diseases and contribute to the progression of heart failure. This review highlights the critical role of IGF-1 and its cognate receptor in cardiac hypertrophy, aging, and remodeling.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ECM Microenvironment in Vascular Homeostasis: New Targets for Atherosclerosis.","authors":"Lu Zhang, Qianqian Feng, Wei Kong","doi":"10.1152/physiol.00028.2023","DOIUrl":"10.1152/physiol.00028.2023","url":null,"abstract":"<p><p>Alterations in vascular extracellular matrix (ECM) components, interactions, and mechanical properties influence both the formation and stability of atherosclerotic plaques. This review discusses the contribution of the ECM microenvironment in vascular homeostasis and remodeling in atherosclerosis, highlighting Cartilage oligomeric matrix protein (COMP) and its degrading enzyme ADAMTS7 as examples, and proposes potential avenues for future research aimed at identifying novel therapeutic targets for atherosclerosis based on the ECM microenvironment.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"39 5","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiology in Perspective.","authors":"Nikki Forrester","doi":"10.1152/physiol.00033.2024","DOIUrl":"10.1152/physiol.00033.2024","url":null,"abstract":"","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"39 5","pages":"246"},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell Membrane Tension Gradients, Membrane Flows, and Cellular Processes.","authors":"Qi Yan, Carolina Gomis Perez, Erdem Karatekin","doi":"10.1152/physiol.00007.2024","DOIUrl":"10.1152/physiol.00007.2024","url":null,"abstract":"<p><p>Cell membrane tension affects and is affected by many fundamental cellular processes, yet it is poorly understood. Recent experiments show that membrane tension can propagate at vastly different speeds in different cell types, reflecting physiological adaptations. Here we briefly review the current knowledge about membrane tension gradients, membrane flows, and their physiological context.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiology in Perspective.","authors":"Nikki Forrester","doi":"10.1152/physiol.00025.2024","DOIUrl":"10.1152/physiol.00025.2024","url":null,"abstract":"","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"39 4","pages":"178"},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of Pathogen and Pesticide Resistance in Honey Bees.","authors":"Leonard J Foster, Nadejda Tsvetkov, Alison McAfee","doi":"10.1152/physiol.00033.2023","DOIUrl":"10.1152/physiol.00033.2023","url":null,"abstract":"<p><p>Bees are the most important insect pollinators of the crops humans grow, and <i>Apis mellifera</i>, the Western honey bee, is the most commonly managed species for this purpose. In addition to providing agricultural services, the complex biology of honey bees has been the subject of scientific study since the 18th century, and the intricate behaviors of honey bees and ants, fellow hymenopterans, inspired much sociobiological inquest. Unfortunately, honey bees are constantly exposed to parasites, pathogens, and xenobiotics, all of which pose threats to their health. Despite our curiosity about and dependence on honey bees, defining the molecular mechanisms underlying their interactions with biotic and abiotic stressors has been challenging. The very aspects of their physiology and behavior that make them so important to agriculture also make them challenging to study, relative to canonical model organisms. However, because we rely on <i>A. mellifera</i> so much for pollination, we must continue our efforts to understand what ails them. Here, we review major advancements in our knowledge of honey bee physiology, focusing on immunity and detoxification, and highlight some challenges that remain.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139974216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary Vascular Dysfunctions in Cystic Fibrosis.","authors":"Jean-Pierre Amoakon, Goutham Mylavarapu, Raouf S Amin, Anjaparavanda P Naren","doi":"10.1152/physiol.00024.2023","DOIUrl":"10.1152/physiol.00024.2023","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is an inherited disorder caused by a deleterious mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Given that the CFTR protein is a chloride channel expressed on a variety of cells throughout the human body, mutations in this gene impact several organs, particularly the lungs. For this very reason, research regarding CF disease and CFTR function has historically focused on the lung airway epithelium. Nevertheless, it was discovered more than two decades ago that CFTR is also expressed and functional on endothelial cells. Despite the great strides that have been made in understanding the role of CFTR in the airway epithelium, the role of CFTR in the endothelium remains unclear. Considering that the airway epithelium and endothelium work in tandem to allow gas exchange, it becomes very crucial to understand how a defective CFTR protein can impact the pulmonary vasculature and overall lung function. Fortunately, more recent research has been dedicated to elucidating the role of CFTR in the endothelium. As a result, several vascular dysfunctions associated with CF disease have come to light. Here, we summarize the current knowledge on pulmonary vascular dysfunctions in CF and discuss applicable therapies.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burning Question: How Does Our Brain Process Positive and Negative Cues Associated with Thermosensation?","authors":"Jose G Grajales-Reyes, Bandy Chen, David Meseguer, Marc Schneeberger","doi":"10.1152/physiol.00034.2023","DOIUrl":"10.1152/physiol.00034.2023","url":null,"abstract":"<p><p>Whether it is the dramatic suffocating sensation from a heat wave in the summer or the positive reinforcement arising from a hot drink on a cold day; we can certainly agree that our thermal environment underlies our daily rhythms of sensation. Extensive research has focused on deciphering the central circuits responsible for conveying the impact of thermogenesis on mammalian behavior. Here, we revise the recent literature responsible for defining the behavioral correlates that arise from thermogenic fluctuations in mammals. We transition from the physiological significance of thermosensation to the circuitry responsible for the autonomic or behavioral responses associated with it. Subsequently, we delve into the positive and negative valence encoded by thermoregulatory processes. Importantly, we emphasize the crucial junctures where reward, pain, and thermoregulation intersect, unveiling a complex interplay within these neural circuits. Finally, we briefly outline fundamental questions that are pending to be addressed in the field. Fully deciphering the thermoregulatory circuitry in mammals will have far-reaching medical implications. For instance, it may lead to the identification of novel targets to overcome thermal pain or allow the maintenance of our core temperature in prolonged surgeries.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":" ","pages":"0"},"PeriodicalIF":5.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}